The present invention relates to physically crosslinked amphiphilic copolymer networks. The present invention more particularly relates to physically crosslinked amphiphilic copolymer networks comprising hydrophobic and hydrophilic segments, methods of preparation and uses thereof, such as for coatings for biological implants.
An amphiphilic polymer network is a random assemblage of hydrophilic and hydrophobic polymer chains that is capable of swelling in both hydrophilic solvents (e.g., water) and hydrophobic solvents (e.g., a liquid hydrocarbon).
Chemically crosslinked amphiphilic polymer networks have been disclosed in the prior art. For example, U.S. Pat. No. 4,486,572 to Kennedy discloses the synthesis of styryl-telechelic polyisobutylene and amphiphilic networks comprising the copolymerization product of the styryl-telechelic polyisobutylene with vinyl acetate or N-vinyl-2-pyrollidone.
U.S. Pat. No. 4,942,204 to Kennedy discloses an amphiphilic copolymer network swellable in water or n-heptane but insoluble in either, comprising the product of the reaction of an acrylate or methacrylate of dialkylaminoalkyl with a hydrophobic bifunctional acryloyl or methacryloyl capped polyelofin. The preferred embodiment discloses an amphiphilic network having been synthesized by free-radical copolymerization of linear hydrophobic acrylate (A-PIB-A) or methacrylate (MA-PIB-MA) capped polyisobutylenes with 2-(dimethylamino)ethyl methacrylate (DMAEMA).
U.S. Pat. No. 5,073,381 to Ivan et al., a continuation-in-part of U.S. Pat. No. 4,942,204, discloses various amphiphilic copolymer networks that are swellable in water or n-heptane that comprise the reaction product of a hydrophobic linear acryloyl or methacryloyl capped polyolefin and a hydrophilic polyacrylate or polymethacrylate, such as N,N-dimethylacrylamide (DMAAm) and 2-hydroxyethyl methylmethacrylate (HEMA).
U.S. Pat. No. 4,085,168 to Milkovich et al. describes chemically joined, phase-separated self-cured hydrophilic thermoplastic graft copolymers which are copolymers of at least one hydrophilic (water soluble) ethylenically unsaturated monomer or mixture thereof and at least one copolymerizable hydrophobic macromolecular monomer having an end group which is copolymerizable with the hydrophilic monomer. The resulting copolymer is a graft copolymer characterized as having a comb-type structure consisting of a hydrophilic polymer backbone with hydrophobic polymer side chains bonded thereto. The side chains are disclosed as being bonded to the hydrophilic polymer at only one end of the side chain, so that no network results.
Some physically crosslinked polymer networks have been described in the prior art. One manner in which to physically crosslink a polymer involves hydrophobic bonding. Hydrophobic bonding refers to the attraction between hydrophobic or nonpolar portions of molecules, causing aggregation of the molecules.
Huglin et al. reported the preparation and characterization of physically crosslinked amphiphilic hydrogels comprised of copolymers of hydrophilic N-vinyl-2-pyrrolidone rich chain segments and hydrophobic methyl methacrylate rich segments. See Preparation and Characterization of some linear copolymers as precursors to thermoplastic hydrogels. Huglin, M. B. et al. Eur. Polym. J. 1994, Vol. 30, 457-463; Effective crosslinking densities and elastic moduli of some physically crosslinked hydrogels. Huglin, M. B. et al. Polymer 1995, Vol. 36, pp. 1 715-1718.
U.S. Pat. No. 5,972,375 to Truter et al. describes a translucent, water-insoluble hydrogel composition comprising a polyvinyl alcohol polymer and a complexing agent, which are physically crosslinked to form a semi-crystalline polyvinyl alcohol-complexing agent polymer complex.
U.S. Pat. No. 6,030,442 to Kabra et al. describes a microporous, fast response, crosslinked gel obtained from a cellulose ether. In one embodiment, the gel is physically crosslinked. The crosslinked gel has sufficient flexibility to enable said gel to be reversibly responsive to change in an environmental condition.
U.S. Pat. Nos. 5, 783,633, 5,786,425 and 5,786,426 to Sperling et al. describe biocompatible polyisoprene-polyurethane interpenetrating polymer network compositions, methods of producing the network compositions and medical devices fabricated from the network compositions. The biocompatible polyisoprene-polyurethane interpenetrating polymer network comprises chemically crosslinked polyisoprene and physically crosslinked polyurethane.
U.S. Pat. No. 5,252,692 to Lovy et al. describes amphoteric acrylic and methacrylic copolymers comprising cationic units of pendant N-substituted amidine and anionic units of acrylic or methacrylic acid carried by substituents of N-acrylamide, N-methacrylamide, N-acrylamidine or N-methacrylamidine. The copolymer networks can be either covalently or physically crosslinked.
U.S. Pat. No. 5,858,264 to Ichino et al describes a composite polymer electrolyte membrane which includes an ion-conductive polymer gel contained and supported by a matrix material of porous polytetrafluoroethylene membrane. An ion-conductive component is prepared by impregnating the porous polytetrafluoroethylene membrane with the polymer containing ion-conductive component and allowing the impregnated material to physically crosslink to form the composite polymer electrolyte membrane.
It is still desirable in the art to provide physically crosslinked amphiphilic copolymer networks having improved properties in relation to the physically crosslinked networks described in the prior art.
It is, therefore, an object of the present invention to provide a physically crosslinked amphiphilic copolymer network.
It is another object of the present invention to provide a method for producing a physically crosslinked amphiphilic copolymer network.
It is another object of the present invention to provide biocompatible coatings for biological implants.
These and other objects, together with the advantages thereof over the copolymer networks and coatings comprising amphiphilic polymer networks of the existing art, which shall become apparent from the specification which follows, are accomplished by the invention as hereinafter described and claimed.
The present invention, therefore, provides a physically crosslinked amphiphilic copolymer network comprising a block copolymer having hydrophobic polyisobutylene segments and hydrophilic poly(alkylene glycol) segments, wherein said polyisobutylene segments are physically crosslinked by hydrophobic forces.
The present invention also provides a process for preparing a physically crosslinked amphiphilic copolymer network comprising: providing a block copolymer comprising hydrophobic polyisobutylene segments and hydrophilic poly(alkylene glycol) segments; introducing the block copolymer into an aqueous solvent; and allowing the block copolymer to self-assemble into physically crosslinked a copolymer network. According to the method of the present invention, the hydrophobic polyisobutylene segments are physically crosslinked by hydrophobic forces.
The present invention further provides biocompatible coatings for implantable biological devices comprising a polymer network comprising hydrophobic polyisobutylene segments and hydrophilic poly(alkylene glycol) segments, wherein said hydrophobic segments of said polymer network are physically crosslinked by hydrophobic forces.